Michael S. Glickman, MD

In this lab

We are broadly interested in the biology of mycobacteria, which include the major human pathogen M. tuberculosis, the nonpathogenic model organismM. smegmatis, and the cancer biotherapeutic agent BCG.

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Mycobacterium as Pathogen, Model System, and Cancer Therapy

Our studies with M. tuberculosis seek to understand the pathways used by this pathogen to cause disease and the host immune response to this persistent infection. We have focused on the biosynthesis of the M. tuberculosiscell envelope, the regulation of that synthesis, and signal transduction across the envelope via regulated intramembrane proteolysis, as well as CD4 T cell responses to Mtb.

We also believe that mycobacteria are a fertile system to study prokaryotic biology, particularly DNA repair. We are studying DNA repair in mycobacteria not only because the host inflicts DNA damage upon the bacterial chromosome during infection, but also because mycobacteria express a unique array of repair pathways (for example, nonhomologous end-joining) not previously described in prokaryotes.

Finally, we study the interaction of BCG with bladder cancer cells. Although used worldwide as a vaccine for M. tuberculosis, BCG is also a highly effective biotherapy for bladder cancer. We are seeking to understand the mechanism of action of BCG in the treatment of bladder cancer, with the ultimate goal of improving its efficacy and predicting which patients will respond to BCG therapy.

At Work: Infectious Diseases Specialist Michael Glickman

BCG

A weakened form of the bacterium (bacillus Calmette-Guérin) that does not cause disease. BCG is used in a solution to stimulate the immune system in the treatment of bladder cancer and as a vaccine to prevent tuberculosis. Also called bacillus Calmette-Guérin.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

biotherapy (BY-oh-THAYR-uh-pee)

Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in biotherapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological response modifier therapy, biological therapy, BRM therapy, and immunotherapy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

bladder (BLA-der)

The organ that stores urine.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

bladder cancer (BLA-der KAN-ser)

Cancer that forms in tissues of the bladder (the organ that stores urine). Most bladder cancers are transitional cell carcinomas (cancer that begins in cells that normally make up the inner lining of the bladder). Other types include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). The cells that form squamous cell carcinoma and adenocarcinoma develop in the inner lining of the bladder as a result of chronic irritation and inflammation.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cell (sel)

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

chromosome (KROH-muh-some)

Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

DNA

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

efficacy (EH-fih-kuh-see)

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

fertile (FER-til)

Able to produce children.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

immune response (ih-MYOON reh-SPONTS)

The activity of the immune system against foreign substances (antigens).

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

infection (in-FEK-shun)

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

organism (OR-guh-NIH-zum)

A living thing, such as an animal, a plant, a bacterium, or a fungus.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

physician (fih-ZIH-shun)

Medical doctor.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

signal transduction (SIG-nul tranz-DUK-shun)

The process by which a cell responds to substances in its environment. The binding of a substance to a molecule on the surface of a cell causes signals to be passed from one molecule to another inside the cell. These signals can affect many functions of the cell, including cell division and cell death. Cells that have permanent changes in signal transduction molecules may develop into cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

T cell (... sel)

A type of immune cell that can attack foreign cells, cancer cells, and cells infected with a virus. T cells can also help control immune responses. A T cell is a type of white blood cell. Also called T lymphocyte and thymocyte.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

therapy (THAYR-uh-pee)

Treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

vaccine (vak-SEEN)

A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

will (wil)

A legal document in which a person states what is to be done with his or her property after death, who is to carry out the terms of the will, and who is to care for any minor children.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)